Injectable polyamide-amine dendrimer-crosslinked meloxicam-containing poly-γ-glutamic acid hydrogel for prevention of postoperative tissue adhesion through inhibiting inflammatory responses and balancing the fibrinolytic system.

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from âˆ¼ 57.31 kPa to âˆ¼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of âˆ¼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.

Meloxicam emulgel potently suppressed cartilage degradation in knee osteoarthritis: Optimization, formulation, industrial scalability and pharmacodynamic analysis.

BACKGROUND AND OBJECTIVE: Meloxicam (MLX) is prescribed for the management of pain and inflammation allied with osteoarthritis (OA). However, MLX causes intestinal damage in long term administration. Hence, meloxicam loaded emulgel (MLX-emulgel) was optimized, formulated and examined under stringent parameters in monosodium-iodoacetate (MIA) induced knee OA in Wistar rats. METHODS AND RESULTS: Nanoemulsion of MLX was fabricated by ultrasonication and microfluidization method with a droplet size of 66.81 ± 5.31-nm and zeta potential of -24.6 ± 0.72-mV. Further, MLX nanoemulsion was optimized with centrifugation, heating-cooling cycles and transmittance parameters in addition to scale-up feasibility with microfluidizer. Post optimization, MLX-nanoemulsion was tailored as emulgel with Carbopol Ultrez 10 NF and assessed for pH, rheology, textural properties, assay and stability features. The in-vitro release study revealed the Korsmeyer-Peppas release kinetics and ex-vivo skin permeation was improved by 6.71-folds. The skin distribution of MLX-emulgel evinced the transfollicular mode of permeation. In-vivo study indicated the protective action of MLX-emulegl expressed in terms of inflammatory cyctokines level, X-ray analysis of knee joints of rats, histopathology and OARSI (Osteoarthritis Research Society International) scoring. MLX-emulgel treated group displayed lower (P < 0.001) level of COX-2 intensity as compared to positive control group. However, it was comparable (P > 0.05) to the normal control group, MLX oral dispersion, i.v. solution and etoricoxib gel groups. MLX-emulgel showcased an alternative to the long term usage of analgesics for relieving the symptoms of knee OA. CONCLUSION: MLX-emulgel may be a potential candidate for translating in to a clinically viable dosage form in the management of knee OA.

Preclinical studies of a high drug-loaded meloxicam nanocrystals injection for analgesia.

Meloxicam (MLX) is considered to have significant analgesic properties. However, the analgesic effects of MLX are compromised by its poor water solubility and thus the low drug loading. The purpose of this study was to develop a high drug-loaded MLX injection by formulating it into nanocrystals (NCs) for the treatment of analgesia. The developed MLXNCs exhibited satisfactory particle sizes and remarkably in vitro dissolution behaviors. In addition, the plasma concentrations of MLXNCs were comparable with the MLX solution (formulated with 1.0% polyoxyethylene castor oil 35) in rats. The acetic acid-induced writhing tests, hot plate tests and hind paw incision experiments demonstrated that the MLXNCs had significant analgesic effects. The findings provide insights into the developed high drug-loaded MLXNCs and provide new therapeutic options for acute and chronic pain management.

The Evaluation of Meloxicam Nanocrystals by Oral Administration with Different Particle Sizes.

Meloxicam (MLX) is a non-steroidal anti-inflammatory drug used to treat rheumatoid arthritis and osteoarthritis. However, its poor water solubility limits the dissolution process and influences absorption. In order to solve this problem and improve its bioavailability, we prepared it in nanocrystals with three different particle sizes to improve solubility and compare the differences between various particle sizes. The nanocrystal particle sizes were studied through dynamic light scattering (DLS) and laser scattering (LS). Transmission electron microscopy (TEM) was used to characterize the morphology of nanocrystals. The sizes of meloxicam-nanocrystals-A (MLX-NCs-A), meloxicam-nanocrystals-B (MLX-NCs-B), and meloxicam-nanocrystals-C (MLX-NCs-C) were 3.262 ± 0.016 µm, 460.2 ± 9.5 nm, and 204.9 ± 2.8 nm, respectively. Molecular simulation was used to explore the distribution and interaction energy of MLX molecules and stabilizer molecules in water. The results of differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) proved that the crystalline state did not change in the preparation process. Transport studies of the Caco-2 cell model indicated that the cumulative degree of transport would increase as the particle size decreased. Additionally, plasma concentration-time curves showed that the AUC0-∞ of MLX-NCs-C were 3.58- and 2.92-fold greater than those of MLX-NCs-A and MLX-NCs-B, respectively. These results indicate that preparing MLX in nanocrystals can effectively improve the bioavailability, and the particle size of nanocrystals is an important factor in transmission and absorption.

Formulation and Evaluation of Baclofen-Meloxicam Orally Disintegrating Tablets (ODTs) Using Co-Processed Excipients and Improvement of ODTs Performance Using Six Sigma Method.

PURPOSE: This study aimed to formulate an orally disintegrating tablet (ODT) containing both baclofen and meloxicam together for treating osteoarthritis. METHODS: Direct compression method was used to prepare ODTs using three types of co-processed excipients (Prosolv ODT G2®, F-melt®, and Pharmaburst®500). ODTs were evaluated according to weight variation, thickness, friability, hardness, drug content, wetting time, in-vitro disintegration time, in-vitro dissolution test, and palatability. To enhance the in-vitro dissolution of meloxicam and palatability of ODT, a six sigma methodology was used, and an improvement phase was established where ODTs were prepared using lyophilization and levigation techniques. Finally, a pharmacokinetic study of the improved ODT was accomplished in comparison to the conventional oral tablet. RESULTS: Pharmaburst-based formula (F4) showed the shortest wetting time and, consequently, the shortest disintegration time and the highest percentage of drug dissolved within 3 min compared to the other formulae. All the improved ODTs had a bitterness taste score vary from (0) palatable and (+1) tasteless. The current sigma level was 3.628 σ and 3.33 σ for palatability and solubility of ODT, respectively, which indicated the process was successfully improved compared with the previous sigma level of 2.342 σ of both processes. Pharmacokinetic study of the improved ODTs showed a significant decrease of Tmax to 120 and 30 min instead of 180 and 120 min for meloxicam and baclofen, respectively. CONCLUSION: ODTs were successfully improved using the six sigma methodology, the pharmacokinetic parameters of both drugs were enhanced due to rapid absorption through the oral mucosa.

Meloxicam and Study of Their Antimicrobial Effects against Phyto- and Human Pathogens.

Recently, the design of new biological metal-ligand complexes has gained a special interest all over the world. In this research, new series of mixed ligand complexes from meloxicam (H2mel) and glycine (Gly) were synthesized. Structures of the compounds were investigated employing elemental analyses, infrared, electronic absorption, 1H NMR, thermal analyses, effective magnetic moment and conductivity. The estimated molar conductivity of the compounds in 1 × 10-3 M DMF solution indicates the non-electrolyte existence of the examined complexes. Additionally, the effective magnetic moment values refer to the complexes found as octahedral molecular geometry. The data of the infrared spectra showed the chelation of H2mel and Gly with metal ions from amide oxygen and nitrogen of the thyizol groups of H2mel and through nitrogen of the amide group and oxygen of the carboxylic group for Gly. Thermal analyses indicated that the new complexes have good thermal stability and initially lose hydration water molecules followed by coordinated water molecules, Gly and H2mel. The kinetic parameters were calculated graphically using Coats-Redfern and Horowitz-Metzeger methods at n = 1 and n ≠ 1. The density functional theory (DFT) calculations were performed at B3LYP levels. The optimized geometry of the ligand and its complexes were obtained based on the optimized structures. The data indicated that the complexes are soft with η value in the range 0.114 to 0.086, while η = 0.140 for free H2mel. The new prepared complexes were investigated as antibacterial and antifungal agents against some phyto- and human pathogens and the minimum inhibitory concentration (MIC) data showed that complex (A) has the lowest MIC for Listeria and E. coli (10.8 µg/mL).

Application of pulsed laser ablation (PLA) for the size reduction of non-steroidal anti-inflammatory drugs (NSAIDs).

We studied the application of pulsed laser ablation (PLA) for particle size reduction in non-steroidal anti-inflammatory drugs (NSAIDs). Grinding of the poorly water-soluble NSAID crystallites can considerably increase their solubility and bioavailability, thereby the necessary doses can be reduced significantly. We used tablets of ibuprofen, niflumic acid and meloxicam as targets. Nanosecond laser pulses were applied at various wavelengths (KrF excimer laser, λ = 248 nm, FWHM = 18 ns and Nd:YAG laser, λ1 = 532 nm/λ2 = 1064 nm, FWHM = 6 ns) and at various fluences. FTIR and Raman spectra showed that the chemical compositions of the drugs had not changed during ablation at 532 nm and 1064 nm laser wavelengths. The size distribution of the ablated products was established using two types of particle size analyzers (SMPS and OPC) having complementary measuring ranges. The mean size of the drug crystallites decreased from the initial 30-80 µm to the submicron to nanometer range. For a better understanding of the ablation mechanism we made several investigations (SEM, Ellipsometry, Fast photography) and some model calculations. We have established that PLA offers a chemical-free and simple method for the size reduction of poorly water-soluble drugs and a possible new way for pharmaceutical drug preformulation for nasal administration.

A novel combination of Soluplus®/Poloxamer for Meloxicam solid dispersions via hot melt extrusion for rapid onset of action. Part 2: comparative bioavailability and IVIVC.

OBJECTIVE: Bioavailability of Meloxicam (MLX) from solid dispersions (SDs), against innovator product Mobic® in humans was conducted. Furthermore, to establish a good in vitro-in vivo correlation (IVIVC); dissolution studies were carried-out in different media. METHODS: MLX/SDs was prepared using Soluplus/Poloxamer via hot-melt-extrusion (EXT-SD) and fusion melt (FUS-SD) techniques. A single oral dose (15 mg), three periods, crossover study of MLX/SDs and Mobic® in four healthy humans under fed conditions was carried-out. In vitro dissolution was studied in pH 1.2, distilled water (pH 6.4), and biorelevant simulated gastric media in pre- and post-prandial states. Level A IVIVC was carried-out by comparing time-scaled fraction dissolved versus fraction absorbed and calculated using the Wagner-Nelson method. Multiple level C models were developed for C max and AUC0-96 versus % dissolved at different time-points. Internal predictability was evaluated for both IVIVC models. RESULTS: MLX rate of absorption (T max) from EXT-SD, FUS-SD, and Mobic® was 1.5, 3.0, and 4.0 h, respectively. Moreover, 1.45- and 1.40-folds increase in AUC0-∞ and C max, was obtained for EXT-SD versus Mobic®, respectively, while FUS-SD gave the lowest extent of drug absorption. EXT-SD provided highest dissolution profiles in all studied media. IVIVC models showed linear-regression (R 2≥0.90) and prediction errors (≤10%) in water and post-prandial simulated gastric media. CONCLUSION: Hot-melt-extrusion technology promises an ideal alternative for enhancing MLX extent of absorption compared to Mobic® with T max value almost equal to the reported intramuscular injection. Predictive IVIVC was established for in vitro dissolution profile and in vivo performance.

Synthesis and characterization of meloxicam eutectics with mandelic acid and saccharin for enhanced solubility.

Meloxicam (MLX) is a non-steroidal anti-inflammatory which is practically insoluble in water, requiring high concentrations to reach therapeutic levels and causing frequently gastrointestinal effects. In this way, the aim of this study was to synthesize two eutectic mixtures of MLX with mandelic acid (MND) and saccharin (SAC) by liquid-assisted grinding resulting in a multicomponent material with enhanced solubility. Mixtures were studied in different stoichiometric and eutectic point was found for each eutectic by Binary phase diagram and Tamman's triangle, with 0.33 molar fraction of MLX for SAC and MND. Eutectics were characterized by thermoanalytical techniques (TG-DSC, EGA, DSC, and DSC microscopy), infrared spectroscopy, and X-ray powder diffraction. Thermal behavior was studied and videos of the materials being heated were available. A polymorphic transition was discovered and studied for MLX-MND eutectic. Each new system was evaluated by solubility, dissolution, and hygroscopicity tests. Eutectics showed an increase in solubility of 1.7× (MLX-MND1), 3.1× (MLX-MND2), and 1.3× (MLX-SAC) with slower dissolution profile when compared with MLX. All new solid forms showed high hygroscopicity at 98% relative humidity with 27.9 and 58.9% increase in mass at day four for MLX-SAC and MLX-MND, deliquescence occurs at day 6. The experiments and analysis in this study help to understand the behavior of eutectics and evaluate them as an approach to modify properties in drugs.

Meloxicam Carrier Systems Having Enhanced Release and Aqueous Wettability Prepared Using Micro-suspensions in Different Liquid Media.

One of the conventional methods of alleviating the problem of poor drug solubility is the particle size reduction. The efficiency of this approach depends on successful formulation suppressing the drug agglomeration. The aim of this study was to circumvent the dissolution problems of model hydrophobic meloxicam drug (MLX) by using liquid media of different wetting capacity to comminute and formulate a rapidly dissolving carrier system without the use of surfactants. Micro-suspensions of MLX were prepared by ball milling, using water or n-Heptane as a liquid medium. The suspensions were used as granulation liquids to formulate granulate from microcrystalline cellulose and lactose mixture. The release kinetics from prepared granulates were studied using the USP-4 dissolution apparatus. Micro-suspensions prepared via wet milling in non-water liquid media exhibited a massive improvement of release rate compared with source meloxicam and they outperformed their water-milled counterparts. The release rates from those formulations, despite not comprising any surfactant, were comparable to those obtained by different authors using surfactant stabilized nanosuspension formulations. Thus, they can present an interesting formulation alternative for hydrophobic drugs that are dissolution limited.

Smart phase transformation system based on lyotropic liquid crystalline@hard capsules for sustained release of hydrophilic and hydrophobic drugs.

Smart phase transformation systems@hard capsule (SPTS@hard capsule) based on lyotropic liquid crystalline (LLC) were developed for oral sustained release in this study. Doxycycline hydrochloride (DOXY) and meloxicam (MLX) were used as hydrophilic and hydrophobic model drug, respectively. Two systems were added with different additives, that is, gelucire 39/01, PEG 1000 and Tween 80 to adjust their melting point and release profiles. The phase transformation of these systems could be triggered by water as well as temperature. They could spontaneously transform into cubic phase or hexagonal phase when coming across with water, to achieve the 24 h sustained release profile. In addition, the obtained systems could switch between semisolid state and liquid state when temperature changed within room temperature and body temperature, which facilitated the phase transformation in gastrointestinal tract and during their encapsulation into hard capsules. LLC-based SPTS@hard capsule revealed potential for the industrialization of its oral administration on account of its drugs accommodation with different solubility, controllable release profile and simple preparation process.

Formulation design, characterization and in vitro drug release study of orodispersible film comprising BCS class II drugs.

Fast dissolving orodispersible film (ODF) was prepared for concurrent administration of biopharmaceutical classification system (BCS) class II drugs, i.e., meloxicam (MX) and tizanidine (TZ), using natural (xanthan gum), semisynthetic (hydroxypropyl methylcellulose and hydroxyethyl cellulose) and synthetic (polyvinyl alcohol) polymers. Compatibility of the ingredients of ODFs was ascertained through Fourier transform infra-red spectroscopy and differential scanning calorimetry. ODFs were characterized through disintegration time, pH of the surface of film, tensile strength, folding endurance, % elongation and content uniformity (MX and TZ) which were found in the range between 17±1.3-56±3.1 s, 5.11±0.07-6.28±0.05, 14.721±1.2-33.084±3.1 N/m2, > 100, 3.33±0.53-10.04±0.77 % and 98.01-99.34 % (MX) and 97.48-99.03 % (TZ), respectively. The values of moisture uptake, moisture loss and loss on drying of all formulations were in the range from 1.06±0.09-7.51±0.93 %, 0.06±0.01-2.3±0.08 % and 0.008±0.002-0.03±0.03 %, respectively. In vitro drug release study in simulated saliva fluid of pH 7.4 has shown that > 90 % MX and TZ was released within 5 min. Visual inspection, scanning electron microscope and X-ray diffraction analysis of all ODFs expressed their smooth surfaces. ODF prepared from xanthan gum (F5) exhibited better physicochemical and mechanical properties as compared to other formulations.

Digital UV/VIS imaging: A rapid PAT tool for crushing strength, drug content and particle size distribution determination in tablets.

The Process Analytical Technology (PAT) and the Quality-by-Design (QbD) approaches can efficiently facilitate the shift to the desired continuous manufacturing and real time release testing (RTRT). By this, it is vital to develop new, in-line analytical methods which fulfil the pharmaceutical requirements. The fast-developing digital imaging-based machine vision systems can provide revolutionary solutions not just in the automotive industry but in the pharmaceutical technology, as well. This study aimed to explore the capabilities of UV/VIS-based machine vision in tablet inspection as a PAT tool for the determination of compression force and crushing strength, drug content and drug distribution in tablets using meloxicam a yellow model drug. In the case of determining the compression force and crushing strength, the application of multivariate wavelet texture analysis (MWTA) based models provided relatively low prediction errors. To predict the drug content of meloxicam tablets CIELAB or RGB colorspace based algorithms were successfully developed and validated. UV/VIS imaging was also used to map the particle size distribution and spatial distribution of meloxicam, the results were compared to chemical maps obtained by Raman microscopy. Digital imaging combined with multivariate data analysis might be a valuable, high throughput, in-line PAT tool for automated inspection of pharmaceutical tablets.

Study of Top-down and Bottom-up Approaches by Using Design of Experiment (DoE) to Produce Meloxicam Nanocrystal Capsules.

In order to investigate the correlation among energy input-related, drug-related, and stabilizer-related aspects for both top-down and bottom-up nanocrystal production, meloxicam nanosuspensions (NS) were produced by using three different methods (low-energy wet milling, high-pressure homogenization, and precipitation) and each method was optimized by using design of experiment (DoE). Box-Behnken design of 3 factors and 3 levels was applied for the optimization of each method. All the three models were found to be significant and the optimized process parameters were used for production of NS, respectively. Interestingly, by comparison of the top-down and bottom-up approaches, the influence of energy input (homogenization pressure or milling speed) from the instruments seemed not significant for top-down compared with bottom-up for this drug. Different mechanisms of homogenization (relatively high energy zone) and milling (relatively low energy zone) led to obtained various significant correlations for each method. Capsules containing nanocrystals were successfully produced by using a novel method applying NS (after wet bead milling and homogenization processes) as wetting agent for direct capsuling and showed superiority regarding as dissolution rate compared with the traditional two-step method (freeze-dried powder used for capsuling as the first step). Different NS preparation methodologies proved to have a direct influence on the following capsuling process and consequently, in the dissolution rate. This study also proved that residual DMSO in nanosuspension after precipitation process could affect the freeze-drying process, which might further alter the redispersion and influence the downstream processes.

Effective delivery of mitomycin-C and meloxicam by double-layer electrospun membranes for the prevention of epidural adhesions.

Epidural adhesion between the spinal dura and the surrounding fibrous tissue often occurs post-laminectomy, resulting in clinical symptoms such as nerve compression and severe pain. In this study, we report a drug-loaded double-layered electrospun nanofiber membrane to prevent the occurrence of epidural adhesion. The nanofibers in both layers are made of a mixture of polycaprolactone (PCL) and chitosan (CS) but at different weight ratios. The bottom layer contacting to the spinal dura is loaded with meloxicam (MX) to prevent inflammation. The top layer that contacts to the fibrous tissue is doped with mitomycin-C (MMC) to inhibit the synthesis of DNA and collagen. The two types of drugs are released from the double-layered membrane within about 12 days. Meanwhile, the membrane can inhibit fibroblasts proliferation in vitro while show no cytotoxicity. In a rabbit laminectomy model, the double-layered membrane can effectively prevent the epidural adhesion formation based on the adhesion scores, histological and biochemical evaluations. The combination release of MX and MMC can signally reduce the inflammation reaction and collagen I/III expression relative to the case with the membranes loaded with only either one type of the drugs. This approach offers new progresses in constructing dual drug delivery system and provides innovative barrier strategy in inhibiting epidural adhesion post-laminectomy.

Transformation of Meloxicam Containing Nanosuspension into Surfactant-Free Solid Compositions to Increase the Product Stability and Drug Bioavailability for Rapid Analgesia.

PURPOSE: The aim of this work was to study the influence of solidification of meloxicam (Mel) containing nanosuspension (nanoMel) on the physical stability and drug bioavailability of the products. The nanoMel sample had poly(vinyl alcohol) (PVA) as a protective polymer, but no surfactant as a further stabilizing agent because the final aim was to produce surfactant-free solid phase products as well. METHODS: The solidified samples produced by fluidization and lyophilization (fluidMel, lyoMel) were examined for particle size, crystallinity, and in vitro release of Mel compared to similar parameters of nanoMel. The products were subjected to an animal experiment using per oral administration to verify their bioavailability. RESULTS: Mel containing (1%) nanoMel sample was produced by wet milling process using an optimized amount of PVA (0.5%) which resulted in 130 nm as mean particle size and a significant reduction in the degree of crystallinity (13.43%) of Mel. The fluidization technique using microcrystalline cellulose (MCC) as carrier resulted in a quick conversion and no significant change in the critical product parameters. The process of lyophilization required a longer operation time, which resulted in the amorphization of the crystalline carrier (trehalose) and the recrystallization of Mel increased its particle size and crystallinity. The fluidMel and lyoMel samples had nearly five-fold higher relative bioavailability than nanoMel application by oral administration. The correlation between in vitro and in vivo studies showed that the fixed Mel nanoparticles on the surface of solid carriers (MCC, trehalose) in both the artificial gastric juice and the stomach of the animals rapidly reached saturation concentration leading to faster dissolution and rapid absorption. CONCLUSION: The solidification of the nanosuspension not only increased the stability of the Mel nanoparticles but also allowed the preparation of surfactant-free compositions with excellent bioavailability which may be an important consideration for certain groups of patients to achieve rapid analgesia.

Ternary solid dispersion to improve solubility and dissolution of meloxicam.

Background Meloxicam (MLX) is a potent non-steroidal anti-inflammatory drug with poor solubility. Solid dispersion (SD) is an effective formulation strategy to improve the dissolution rate of poorly water-soluble compounds. Hydroxy propyl methyl cellulose (HPMC) as an inert polymer carrier and nicotinic acid (NA) as disturbance can be used as a matrix of SD. The aim of this study was to determine the effect of MLX-HPMC-NA SD on the solubility and dissolution of MLX. Methods SD was prepared by the solvent evaporation technique with methanol being used as a solvent. Methanol was evaporated at room temperature. SD of MLX was prepared involving various matrix compositions at MLX:HPMC:NA ratios of 1:1:1 (SD1), 1:1:2 (SD2), 1:2:1 (SD3), and 1:2:2 (SD4). Results The solubility profile of MLX in SD3 (64.34 ppm) showed a higher improvement than the physical mixture (15.99 ppm) and pure MLX (6.89 ppm). This increase might be due to the formation of molecular dispersion of MLX in the polymer as hydrophilic matrix and NA have both donor-acceptor sites for hydrogen bonding interactions. The dissolution profile of SD3 also showed the highest improvement. The melting endotherm of SD3 was detected at 219.5 °C, in which case it originated from NA rather than from MLX, showing that MLX was molecularly dispersed and amorphous. Conclusions MLX solubility and dissolution profile could be improved by the SD technique with a matrix of HPMC and NA. The best result was given by SD3 with an MLX:HPMC:NA ratio of 1:2:1. Based on the characterization study, it is predicted that hydrophilic polymer and hydrogen bonding interactions play important roles in MLX solubility or dissolution rate improvement.

Improving solubility and dissolution of meloxicam by solid dispersion using hydroxypropyl methylcellulose 2910 3 cps and nicotinamide.

Background Solid dispersion (SD) represents a good method for enhancing the solubility of poorly water-soluble drugs. Meloxicam (MLX), a nonsteroidal anti-inflammatory drug has poor solubility in water. Hydroxypropyl methylcellulose (HPMC) 2910 3 cps, a hydrophilic carrier and nicotinamide (NC), a hydrotropic agent can be used as matrix of SD. The aim of this study is to investigate the effect of HPMC 2910 3 cps and NC as SD matrix on the solubility and dissolution rate of MLX. Methods The SD of MLX was prepared by solvent evaporation method using methanol as solvent. The SD formulations composed of HPMC and NC in different ratios (1:1:1, 1:1:2, 1:2:1, 1:2:2). The physical state of MLX SD were characterized by Differential Thermal Analyzer (DTA), Fourier Transform Infrared Spectroscopy, powder X-ray diffractometer (PXRD), Scanning Electron Microscopy (SEM). The solubility and dissolution of the MLX SD were also evaluated. Results The results of differential thermal analysis (DTA) showed that the melting point of MLX SD was lower than MLX further the X-ray diffractogram showed a decrease of the crystallinity of MLX in SD. Those indicated that MLX was dispersed molecularly in SD. The SD showed a widening transmission peak at 3000-3500 cm-1 which resembled the peak of pure MLX transmission. It indicated that intermolecular hydrogen bonds were formed between MLX, HPMC, and NC. The solubility and the dissolution efficiency (ED60) of SD with MLX-HPMC 2910 3 cps-NC = 1:2:1 increased 3.59 times and 1.50 times higher then MLX substance. Conclusions MLX-HPMC-NC SD system increased the solubility and dissolution of MLX. The SD with MLX-HPMC 2910 3 cps-NC ratio of 1:2:1 had the highest solubility and ED60 compared to the other SD formulas.

Psyllium (Plantago Ovata Forsk) Husk Powder as a Natural Superdisintegrant for Orodispersible Formulations: A Study on Meloxicam Tablets.

(1) Background: In this work, we investigated the application of a natural superdisintegrant, psyllium (Plantago ovata Forsk) husk powder, for the manufacture of orodispersible meloxicam tablets. Meloxicam was chosen as a model compound for the study. (2) Methods: The tablets were prepared using different concentrations of psyllium husk by direct compression. Bulk density, tapped density, hardness, friability, in vitro disintegration, and dissolution time tests were used to assess the quality of the formulations. (3) Results: Psyllium husk powder significantly increased the dissolution rate of meloxicam. The formulation containing 16 mg of psyllium husk powder showed the lowest wetting time, the highest water absorption ratio, and the lowest disintegration time compared to the control and to the other formulations. These effects may be attributed to the rapid uptake of water due to the vigorous swelling ability of psyllium husk powder. (4) Conclusions: The powder could be recommended as an effective natural superdisintegrant for orodispersible formulations.

Sericin Inhibits Devitrification of Amorphous Drugs.

The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The binary solid dispersions comprising varying mass ratios of drug and sericin were subject to amorphization by spray drying, solvent evaporation, ball milling, and physical mixing. Further, obtained solid dispersions (SDs) were characterized by HPLC, ATR-FTIR, H1NMR, molecular docking, accelerated stability study at 40°C and 75 ± 2% RH (XRD and DSC), and in vitro dissolution studies. The HPLC analysis indicated no decomposition of the drugs during the spray drying process. From ATR-FTIR, NMR, and molecular docking study, it was revealed that H-bonding played a vital role in amorphous drug stabilization. An excellent devitrification inhibition was observed in case of lornoxicam (SDLS3) and meloxicam (SDMS3) SDs prepared by spray drying. On the other hand, spray-dried SD of felodipine (SDFS3) showed traces of microcrystals. The percent crystallinity of SDLS3, SDMS3, and SDFS3 was found to be 7.4%, 8.23%, and 18.31% respectively indicating adequate amorphization. The dissolution performance of SDLS, SDMS, and SDFS after 3 months showed > 85% than SDs prepared by other methods. Thus, sericin significantly inhibited crystallization and was responsible for amorphous state stabilization of pharmaceuticals.